EAL

Diabetes and Protein

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this study was to determine whether treatment of hypoglycemia with a snack containing both protein and carbohydrate results in more prolonged protection against subsequent hypoglycemia than ingestion of carbohydrate alone.

Inclusion Criteria:

1. Type 1 diabetes

2. Absence of complications of diabetes

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment: The studies were conducted on the subjects who were inpatients in a clinical research center (GCRC) affiliated with Mayo Clinic, Rochester, MN.

Design: The subjects were made hypoglycemic by insulin infusion and then given 1 of 2 snacks (carbohydrate or carbohydrate + protein) by random assignment. Each subject returned a second day for a study using the alternate snack.

Blinding Used (if applicable): not specified

Intervention (if applicable):

1. Subjects admitted to the GCRC the night before the study and consumed a meal (1800 h) that contained 615 kcal, 50% carbohydrate, 20% protein, 30% fat.

2. Long acting insulin was with held 24-hr before the study.

3. Insulin was infused to maintain blood glucose in the range of 80 to 100 mg/dL.

4. At 0700 h the following morning, insulin was fixed at each subject’s basal rate; the basal insulin infusion was stopped at 0800 h and substituted with the test insulin infusion of 0.49+0.01mU/kg throughout the remainder of the study.

5. The blood glucose was allowed to drop to 50 mg/dL at which time the subjects were given a snack with bread (85 kcal, 15 g carbohydrate) or bread + ham (205 kcal, 15 g carbohydrate + 18 g protein).

Statistical Analysis:

mean ±SEM, with the time of consumption being zero
increments and nadirs were first determined for each individual, then summed to determine group means
rate of fall of plasma glucose concentration v. time following the post snack peak was calculated using linear regression analysis
change in plasma glucagon in response to the the meal was calculated by subtracting the mean glucagon concentration present during the 30 minutes before the initiation of the test insulin infusion from the mean concentration present following food ingestion and multiplying by time

Data Collection Summary:

Timing of Measurements: After subjects consumed the snack, blood was sampled at 10-minute intervals for the first 30 minutes and at 15-minute intervals thereafter.

Dependent Variables

plasma glucose response
plasma insulin response
plasma glucagon response

Independent Variables:

snack consisted of a slice of bread (85 kcal) or a slice of bread plus boiled ham (205 kcal)
all slices of bread were from a single loaf prepared in the Clinical Research Center kitchen
Women were studied at the same stage of the menstrual cycle

Control Variables

Description of Actual Data Sample:

Initial N: 6 subjects , 3 male and 3 female

Final N: 6

Ethnicity: not specified

Age: 34±3 yr

Other relevant demographics:

Duration of diabetes: 11±2 yr
HbA1c: 9.0%±0.5% (normal 4-7%)

Anthropometrics

Location: USA

Summary of Results:

Other Findings

Although bread + meat resulted in a more marked rise (P<0.05) in glucagon than bread alone, neither the post treatment peak glucose concentrations (73±4 vs. 70±6 mg/dL) nor the subsequent rate of fall of glucose (-0.42±0.10 vs. –0.35±0.07 mg/dL/min) differed (NS).

Glucose concentrations were equivalent before (5.0±0.3 vs. 5.2±0.3 mmol/L) and fell to a similar nadir (2.7±0.1 vs. 2.5±0.1 mmol/L) during the test insulin infusions on the bread and bread + meat study days, respectively.

The peak glucose level after eating either the bread or bread+meat snacks were comparable (3.9±0.3 vs. 4.1±0.2 mmol/L).

Insulin concentrations from both before (62±12 vs. 57±7 pmol/L) and during the insulin infusion (143±13 vs. 145±13 pmol/L) were the same on the bread and bread + meat study days.

The mean increment in glucagon above baseline (28±9 vs. –8±7 pg/ml) was greater (P<0.05) following bread+meat than bread alone.

Author Conclusion:

The present experiments demonstrate that treatment of insulin-induced hypoglycemia treated with bread or bread + meat resulted in the same rate of recovery from and duration of protection against subsequent hypoglycemia. Thus, adding protein to the carbohydrate snack increased the number of kcal and it did not appear to provide any additional advantage to the treatment of hypoglycemic individuals.

This study shows no advantage of adding protein to a snack to treat hypoglycemia.

Funding Source:

Government:

US Public Health Service

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Only 6 subjects.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		???
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	No
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		N/A
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	N/A
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	No
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	No
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes